Whole-Brain Functional Network Connectivity Abnormalities in Affective and Non-Affective Early Phase Psychosis

Psychosis disorders share overlapping symptoms and are characterized by a wide-spread breakdown in functional brain integration. Although neuroimaging studies have identified numerous connectivity abnormalities in affective and non-affective psychoses, whether they have specific or unique connectivity abnormalities, especially within the early stage is still poorly understood. The early phase of psychosis is a critical period with fewer chronic confounds and when treatment intervention may be most effective. In this work, we examined whole-brain functional network connectivity (FNC) from both static and dynamic perspectives in patients with affective psychosis (PAP) or with non-affective psychosis (PnAP) and healthy controls (HCs). A fully automated independent component analysis (ICA) pipeline called “Neuromark” was applied to high-quality functional magnetic resonance imaging (fMRI) data with 113 early-phase psychosis patients (32 PAP and 81 PnAP) and 52 HCs. Relative to the HCs, both psychosis groups showed common abnormalities in static FNC (sFNC) between the thalamus and sensorimotor domain, and between subcortical regions and the cerebellum. PAP had specifically decreased sFNC between the superior temporal gyrus and the paracentral lobule, and between the cerebellum and the middle temporal gyrus/inferior parietal lobule. On the other hand, PnAP showed increased sFNC between the fusiform gyrus and the superior medial frontal gyrus. Dynamic FNC (dFNC) was investigated using a combination of a sliding window approach, clustering analysis, and graph analysis. Three reoccurring brain states were identified, among which both psychosis groups had fewer occurrences in one antagonism state (state 2) and showed decreased network efficiency within an intermediate state (state 1). Compared with HCs and PnAP, PAP also showed a significantly increased number of state transitions, indicating more unstable brain connections in affective psychosis. We further found that the identified connectivity features were associated with the overall positive and negative syndrome scale, an assessment instrument for general psychopathology and positive symptoms. Our findings support the view that subcortical-cortical information processing is disrupted within five years of the initial onset of psychosis and provide new evidence that abnormalities in both static and dynamic connectivity consist of shared and unique features for the early affective and non-affective psychoses.

Excess Mortality and Life-Years Lost in People With Schizophrenia and Other Non-affective Psychoses: An 11-Year Population-Based Cohort Study

Psychotic disorders are associated with premature mortality, but research was primarily based on Western countries and rarely examined non-affective psychoses other than schizophrenia (ONAP). This population-based cohort study investigated excess mortality in 46 896 schizophrenia and 20 651 ONAP patients between January 2006 and December 2016 in Hong Kong (HK), by estimating all-cause and cause-specific standardized mortality ratios (SMRs), and life-years lost (LYLs), a recently developed, more precise reduced life expectancy measure taking into account the illness onset (age at first-recorded diagnosis). Changes in mortality metrics over the study period were assessed. Study data were retrieved from a territory-wide medical-record database of public healthcare services to 7.5 million HK residents. Results showed that schizophrenia and ONAP patients had higher all-cause (schizophrenia: SMR: 2.49 [95% CI: 2.43–2.55]; ONAP: 2.00 [1.92–2.09]), natural-cause (1.80 [1.74–1.85]; 1.47 [1.40–1.54]), and unnatural-cause (6.97 [6.47–7.49]; 8.53 [7.61–9.52]) mortality rates than general population. Respiratory diseases, cardiovascular diseases, and cancers accounted for the majority of deaths in patient cohorts. Men and women with schizophrenia had 9.53 years and 8.07 years of excess LYLs, respectively. For ONAP, excess LYLs was 8.18 years for men and 5.44 years for women. The overall mortality gap remained similar for both patient groups over time despite their improved longevity and declined unnatural-cause mortality rates. Taken together, schizophrenia and ONAP are associated with increased premature mortality and substantially reduced lifespan in a predominantly Chinese population, with excess deaths mainly attributed to a natural cause. Persistent mortality gap highlights an urgent need for targeted interventions to improve the physical health of patients with psychotic disorders.

Robert Kendell: his career and contribution to psychiatric diagnosis

This paper reviews the career of Robert Kendell with emphasis on his contribution to diagnosis in psychiatry. His studies on the classification of depression showed that symptoms were distributed on a continuum and that division of depression into sub-types was not justified. Similarly he showed there was no clear-cut distinction between symptoms of schizophrenia and affective psychoses. He examined Scadding’s definition of disease as it applied to psychiatry and questioned whether some conditions such as neuroses and personality disorders would qualify as illnesses. He concluded that available evidence supported a dimensional rather than a categorical approach to diagnosis.

Successful Antiviral Therapy Reduces Risk of Schizophrenia Among Chronic Hepatitis C Patients: A Nationwide Real-World Taiwanese Cohort (T-COACH)

Background Chronic hepatitis C (CHC) has been associated with major psychoses, and interferon (IFN)-based therapy may cause psychiatric sequelae. We aimed to evaluate the effects of sustained virological response (SVR) on the incidence of major psychoses in a nationwide Taiwanese CHC cohort. Methods Fifteen thousand eight hundred thirty-six CHC Taiwanese who received IFN-based therapy were enrolled between 2003 and 2015. Of those, 12 723 patients were linked to the National Health Insurance Research Databases for the incidence of major psychoses. Death before major psychoses was considered a competing risk. Results Twenty-four patients developed new-onset major psychoses during 67 554 person-years (3.6 per 10 000 person-years), including 16 affective psychoses, 7 schizophrenia, and 1 organic psychotic condition. The incidence of major psychoses and affective psychoses did not differ between the SVR and non-SVR groups. The 10-year cumulative incidence of schizophrenia were significantly higher in the non-SVR than in SVR patients (0.14% vs 0.04%, P = .036). Cox subdistribution hazards showed that SVR and older age were associated with a significantly lower risk of schizophrenia (hazard ratio = 0.18 and 0.17). Sustained virological response was associated with decreased incidence of schizophrenia and majorly observed among patients with age <45 (P = .02). Conclusions Successful IFN-based therapy might reduce the incidence of schizophrenia among CHC patients, especially among younger patients.

S133. DIAGNOSED SPEECH, SCHOLASTIC AND MOTOR DISORDERS AS PREDICTORS FOR NON-AFFECTIVE PSYCHOSES

Background Premorbid cognitive impairments are associated with schizophrenia, but little is known about the risk of developing psychoses among children with diagnosed speech, scholastic and motor disorders. Our aim was to study if children diagnosed with these are at increased risk of non-affective psychoses in adolescence and early adulthood. Methods We identified all children born 1996–2001 that were diagnosed with a speech disorder (ICD-10 code F80), scholastic disorder (F81), motor disorder (F82) or mixed developmental disorder (F83) before age 15 in outpatient and inpatient specialized services in Finland by using nationwide registers (n=17,038). A control cohort of children without these disorders was identified (n=63,745). The outcome was non-affective psychoses (F20-F29) diagnosed between age 15 years and the end of year 2017 (maximum age at end of follow-up: 16.0–21.9 years). We used Cox regression to study the association between speech, scholastic and motor disorders and psychoses and adjusted for sex, urbanicity and comorbid depression and conduct disorders. Results A total of 216 and 251 subjects were diagnosed with non-affective psychoses during follow-up in the cohort of speech, scholastic and motor disorders and the control-cohort, respectively. The cumulative incidence of psychoses from age 15.0 to 21.9 years was 2.4 % (95% confidence interval [CI] 2.0 - 2.8 %) in the cohort of speech, scholastic and motor disorders compared to 0.8 % (95% CI 0.7 % - 1.0 %) in the control-cohort (adjusted hazard ratio [aHR] 2.6, 95% CI 2.2 - 3.2). When stratified by a pure or a combination of at least two speech, scholastic and motor disorders, all categories were significantly associated with psychoses with the highest HR for motor disorders (aHR 3.6, 95% CI 2.0 - 6.4), followed by the combination of different speech, scholastic and motor disorders (3.3, 2.4 - 4.4), pure scholastic disorders (2.4, 1.5 - 3.7) and pure speech disorders (1.7, 1.2 - 2.6). Discussion Non-affective psychoses in late adolescence and early adulthood are associated with speech, scholastic and motor disorders diagnosed in childhood, in particular motor development disorders.

Cigarette smoking as a risk factor for schizophrenia or all non-affective psychoses

Background Smoking tobacco is regarded as an epiphenomenon in patients with schizophrenia when it may be causal. We aimed to examine whether smoking status is related to the onset of schizophrenia or the broader diagnosis of non-affective psychosis, including schizophrenia. Methods We used data from The Health Improvement Network primary care database to identify people aged 15–24 between 1 January 2004 and 31 December 2009. We followed them until the earliest of: first diagnosis of schizophrenia (or psychosis), patient left the practice, practice left THIN, patient died or 31 December 2014. Results In men, incidence rates for schizophrenia per 100 000 person years at risk were higher in smoking initiators (non-smoker who became a smoker during the study) than in non-smokers (adjusted IRR 1.94; 95% CI 1.29–2.91) and higher still in smokers (adjusted IRR 3.32; 95% CI 2.67–4.14). Among women, the incidence rate of schizophrenia was higher in smokers than in non-smokers (adjusted IRR 1.50; 95% CI 1.06–2.12), but no higher in smoking initiators than non-smokers. For non-affective psychosis, the pattern was similar for men but more evident in women where psychosis incidence rates were higher in smoking initiators (adjusted IRR 1.90; 95% CI 1.40–2.56) and in smokers (adjusted IRR 2.13; 95% CI 1.76–2.57) than in non-smokers. Conclusions We found an important and strong association between smoking and incidence of schizophrenia. Smoking may increase risk through as yet unknown pathways or smoking may share genetic risk with schizophrenia and non-affective psychoses.